In response to extracellular signaling molecules, progenitor cells either continue dividing without differentiating, in a process termed self-renewal, or divide a limited number of times and then differentiate. Smith et al. find that the redox state of progenitor glial cells correlates with their self-renewal capacity.

A fluorescent dye sensitive to redox state, dihydrotetramethylrosamine (Ros), was used to label and sort oligodendrocyte-type-2 astrocyte cells into one group possessing a relatively reduced intracellular state (Ros-low) and a second with an oxidized intracellular environment (Ros-high). The Ros-low cells exhibited a high proportion of self-renewing or dividing cells, and yielded four times as many cells per clone as those in the Ros-high group. Pharmacological alteration of intracellular redox state to a more reducing potential promoted self-renewal and blocked the ability of extracellular factors to promote differentiation, while adding oxidizing agents to the medium had the opposite effect. Modulation of the intracellular redox state by multiple signaling process may serve to integrate inputs from a collection of pathways that influence differentiation and self-renewal. — NG